title: Levels of circulating CD45(dim)CD34(+)VEGFR2(+) progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors.
abstract: BACKGROUND
  Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45(dim)CD34(+)VEGFR2(+) progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI).
  
  
  METHODS
  Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45(-)CD31(+)CD146(+)7-amino-actinomycin (7AAD)(-) cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1α and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells, plasma factors, as well as day 1-day 14 changes in CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined.
  
  
  RESULTS
  No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cell levels were associated with PFS (P=0.01) and OS (P=0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P=0.03, P=0.002). Changes in VEGF and SDF-1α levels were associated with OS (P=0.02, P=0.007).
  
  
  CONCLUSIONS
  Monitoring CD45(dim)CD34(+)VEGFR2(+) progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome.
authors.affiliation: Translational Research Laboratory, Institut de Cancérologie Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France. farace@igr.fr
authors.forename: F
authors.initials: F
authors.lastname: Farace
authors.forename: M
authors.initials: M
authors.lastname: Gross-Goupil
authors.forename: E
authors.initials: E
authors.lastname: Tournay
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.forename: N
authors.initials: N
authors.lastname: Vimond
authors.forename: N
authors.initials: N
authors.lastname: Jacques
authors.forename: F
authors.initials: F
authors.lastname: Billiot
authors.forename: A
authors.initials: A
authors.lastname: Mauguen
authors.forename: C
authors.initials: C
authors.lastname: Hill
authors.forename: B
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*
chemical_list: D018952:Antigens, CD34; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human